Safening agents for dinitrophenols and their derivatives

ABSTRACT

THE PHYTOTOXICITY OF PESTICIDAL FORMULATIONS CONTAINING DINITROPHENOLS, OR THEIR DERIVATIVES, IS REDUCED ON HOST CROP PLANTS, SUCH AS CUCURBITS, GRAPES, BEANS AND TOMATO BY ADDING TO THE FORMULATION SAFENING AGENTS SELECTED FROM A THIOUREA, A THIURONIUM SALT, A TETRAZOLIUM SALT, AND CERTAIN INIDAZOLINES. THE SAFENING AGENTS PREVENT INTERNAL TISSUE DAMAGE IN GROWING PLANTS CAUSED BY THE DIMITROPHENOLS AND DERIVATIVES WITHOUT REDUCING THEIR FUNGICADAL ACTIVITY.

United States Patent 3,659,017 SAFENING AGENTS FOR DINITROPHENOLS AND THEIR DERIVATIVES William C. von Meyer, Willow Grove, Pa., assignor to Rohm and Haas Company, Philadelphia, Pa. No Drawing. Continuation-impart of application Ser. No. 648,995, June 26, 1967. This application Sept. 23, 1969,

Ser. No. 860,412

Int. Cl. A01n 9/20 US. Cl. 424-326 Claims ABSTRACT OF THE DISCLOSURE The phytotoxicity of pesticidal formulations containing dinitrophenols, or their derivatives, is reduced on host crop plants, such as cucurbits, grapes, beans and tomato by adding to the formulation safening agents selected from a thiourea, a thiuronium salt, a tetrazolium salt, and certain imidazolines. The safening agents prevent internal tissue damage in growing plants caused by the dinitrophenols and derivatives without reducing their fungicidal activity.

This application is a continuation-impart of US. Ser. No. 648,995, filed June 26, 1967, now abandoned. i This invention relates to safening a host crop plant against injury caused by pesticidal formulations that are applied to the locus of the host plant and particularly to the foliage of the host plant in order to control certain pathogens and insects that cause the host plant to be are useful as pesticides. Their use, however, entails a serious disadvantage because they may produce an unacceptable level of injury to plants. This prevents the wide use of simple nitrophenols, moreover, certain of their esters useful as foliar fungicides and insecticides may sometimes also show objectionable phytotoxicity, particularly at high temperatures.

Attempts at reducing the injury to the plants caused by the external application of chemicals have thus far been limited to controlling factors external to the plants tissues. Some of the prior art attempts include: a reduction of the dosage of active material per unit area on the plant surface; the use of spreading agents which prevent the toxicant from aggregating on small areas of 'the plant surface; manipulation of pH in order to maintain an anionic form rather than the neutral form of the toxiwood bark as carrier materials for dinitrophenols (see- US. Pats. 2,166,121 and 2,166,122); the formation of cyclohexyl amine addition salts of 2,4-dinitrosubstituted phenols which are less injurious to plants than the free phenol (see US. 2,225,619); the mixing of an inert diluent with an amine salt of a dinitrophenol to provide an even safer pesticidal composition (see US. 2,365,056);

the incorporation of methyl cellulose to amine salts of 3,659,017 Patented Apr. 25, 1972 dinitroalkylphenols to reduce injury to citrus fruitsfrom that of commercially objectionable levels to a safe level (see US. 2,745,782). 5

In accordance with this invention injury to plant tissues caused by the external application of pesticidal formulations containing dinitrophenols, or their derivatives, has been effectively reduced by the addition of certain safen ing agents to the pesticidal formulation. It has been discovered that tissue damage in growing plants caused by the external application of the substituted dinitrophenol formulations can be, reduced up to about ninety-five percent by incorporating into the formulation at least one compound (referred to hereinafter as safening agent) selected from I (a) 1-cyclohexyl-3- 2-morpholinyl- (4) -ethyl) -t hiourea, (b) S-t-octylcresoxyethoxyethyl-N,N'-dimethyl thinronium chloride, (c) 2,3,S-triphenyltetrazolium chloride, (d) 2-tetradecylmercapto-A -imidazoline hydrobromide, (e) Z-cetyhnercapto-A -imidazoline hydrobromide, (f) 1-acetyl-2-benzylmercapto-A -imidazoline, and (g) Z-(B-hydroxyethylmercapto)A -imidazo1ine hydrochloride.

These safening agents are either products of commerce or may be made by the methods given below:

(a) 1-cyclohexyl-3-(2-morpholinyl (4) ethyD-thiourea is commercially available from Aldrich Chemical 00., inc, Milwaukee, Wis.

(b) S-t-octylcresoxyethoxyethyl N,N' dimethylthiuronium chloride was prepared by the following reaction methylthiuronium chloride.

(0) 2,3,S-triphenyltetrazolium chloride is commercially available from Distillation Products Industries, Rochester, New York. r

(d) Z-tetradecylmercapto-A unidazoline hydrobromide was prepared by the following reaction A mixture of ethylene thiourea (11 g., 0.18 mole),

'rnyrestyl bromide (30 g., 0.18 mole) and ethanol (50 ml.) was heated under reflux for 15 hours. The solvent was removed under reduced pressure to give 41 g. of a colorless, waxy solid which melted at l44 C. This was found by analysis to contain 7.5% N; calculated for C H BrN2S is 7.4% N, The product was a quantitative;

yield of 2:tetradecylmercaptoh -imidazoline hydrobrd of white solid melting a't '9294' C. This was found by analysisto contain 6.9% N; calculated for c sn arms is 619% The product was a 75% yield of Z-acetylmercapto-h' imidazoline hydrobromide. I (f) l-acetyl-Z-benzylmercapto-n -imidazoline was prepared'bythe following series of reactions acetic anhydride I CHzN O=C CH3 A reaction mixture consisting of ethylene thiourea (51 g., 0.5 mole), benzyl chloride. (63 g., 0.5 mole) and ethanol (300 ml.) 'Was heated at reflux temperature for 3 hrs. then concentrated to give 150 g. of syrup. To this was added 50 ml. of 2 N-HCl in 250 ml. of water and most of the syrup dissolved. The mixture was extracted with benzene and the aqueous layerwas neutralized with 325 ml; of 2"N-NaOH. The resulting solid was filtered off, washed with water and oven' dried to give 80 g. meltin-g'at-64-65 C. This'was an 83% yield of Q-benzyl-mercapto A -irnidazoline.

{To 2-benz yhnercapto-A -iniidazoline (38.5 'g.-, 0.2-rnole) was added acetici-anhydride ('51 .g., 0.5 mole). An exo thermic reaction resulted ina solution. Benzene (25 ml.) was added and 'thesolution cooled to give a solid which was recrystallized from methanol (50 ml.) to give 23 g. of -white solid melting at- 117-118 C. The reaction filtrate was concentrated to give .g.1 of residue which was recrystallized from the above methanol :filtrate to give 1.5 .:gWof-sol-id' meltingat 1.1-3-1-16 C. These products amounted to an 80% yieldofl-a'cetyl-Z-benzylmercapton -imidazoline.

(g) 2-(fi-hydroxyethylmercapto)-A -imidaz0line hydrochloride was prepared by the following reaction CHZNH C=S OlCHzCHgOH A reaction mixture consisting of .ethylenethiourea (102 g., Imole) and.ethylenezchlorohydrin (80.5 g.-, lmole) was heated on a steam bath for 4.5 hrs. Ethanol (200 ml.)

uwasadded-to give-a white solid which was removed by l filtration and amounted to 61 g. The filtrate was concentrated to give 91 g. of yellow syrup and this was found to contain by analysis 16.1% N; calculated for C H Cl-N OS is 15.4% N. The syrup is a 50% yield of 2 6=hydroxyethylmerlcapto)-A -imidazoline hydrochloride.

The safening agentsof this invention are incorporated into the subs'tituted-dinitrophenol formulation in a Weight ratio of safening agent to dinitrophenol, or derivative, of from about 1:12 to about 3:1; a range of" from about 1:4 to about 1.5:1 is preferred. The amount of safening agent required to reduce or eliminate the injury caused by the dinitrophenols varies with the particular dinitrophenol, the particular safening agent and the host plant. Therefore, the amount of safening agent needed 'to reduce theinjury .to a commercially acceptable level on sensitive crops will depend upon the particular circumstances. The

mechanism by which the internal safening agents of this invention operates is not understood because the host plant may act 'on the chemical compounds that are introduced intoit. As soon as the safening agent enters the plant it is subject tothe plants metabolic system. Therefore, it cannot be stated with any degree of certainty that the exact structure introduced into the plant is responsible for the safening efiect.

The safening agents of this invention permit the exposure of extremely sensitive plants to dinitrophenols, or

their derivatives. For example, it may now be possible for cucurbits and certain fruits to obtain insecticidal benefits from simple dinitrophenols. In addition, it is now possible to use higher dosages of the dinitrophenols that were formerly phytotoxic, and certain commercial pesticides may now be used in applications that were formerly impossible because of crop injury.

-An importantaspect of this invention is that the above defined safening agents prevent internal tissue damage in growing plants caused by the external application of biocidal formulations containing dinitrophenols without significantly reducing their pesticidal activity. .In addition, the safening agents are themselves non-toxic at eifective rates of application.

The present invention is applicable to substituted dinitrophenols andv their esters wherein the phenol is represented by-the formula:

wherein n is 1 or 2 and Y is an alkyl group having up to 16 carbon atoms with the proviso that when n is 2, the 2 alkyl groups shall total no more than 24 carbon atoms, cycloal-kyl, isoborn'yL-phenyl and benzyl. The nitro groups are preferably in any two" of the 2, 4 and 6 positions so that when n is 2, it is preferred that at least one of the Y substituents be in the 3 or 5 position. It'is preferred to use compounds characterized by the above formula wherein Y is alkyl and it is most preferred to use-dinitrophenols wherein Yi's alk-yl, n is 1 and the'nitro groups are in any two of the 2, 4 and 6 positions. The nature of the ester group is not critical for purposes of this invention and any acid or acid precursor taught by the art as giving a biologically useful ester may be used. The most Widely usedesters are the alkanoates as the acetates; the alkenocarbonates as-the C to C alkyl carbonates.

The compounds as. described above have long been known to be outstanding biocides. However, the phenols are also generally characterized by an accompanying phytotoxicity which limits their usefulness on plants. It is believed that the phytotoxicity of the free phenols is associated with the presence of the phenolic hydroxyl group and that, insofar as the esters of the phenols display phytotoxicity, the property is caused by the presence of a minor amount of the free phenol as possibly by the hydrolysis of the ester under use conditions. Thus, 'while the biocidal effectiveness of the compounds is largely determined by the nature and position of the substituent groups in the dinitrophenol, the phytotoxicity of the compound is primarily determined by the presence of the phenolic hydroxyl group. The compounds described herein as safening agents have been found to significantly reduce the phytotoxicity of the substituted-dinitrophenols and their esters described herein irrespective of the nature of the substituent groups. The following compounds are representative substituted dinitrophenols: 2,4 dinitro-6-sec. butylphenol, dinitrocaprylphenol, 2 i-bornyl-4,6-dinitrophenol, 2,4-dinitro-6-(C C )alkyl phenols such as 2,4- dinitro 6-nonylphenol, 2,6-dinitro-p-cresol, 2,6-dinitro-4- (1-ethylhexyl)phenol, 2,4-dinitro-6-( l-ethylhexyl) phenol, 2,4 dinitro-6-(l-methy1heptyl)phenol, 2,6-dinitro-4-(lmethylhexyDphenol, 2,6 dinitro-4-(l-propylpentyl)phenol, 2,6-dinitro-4-(C -C )alkyl phenols, 2,4-dinitro-3,5- dimethylphenol, 2,4-dinitro-3-methyl-fi-dodecylphenol, 2, 4 dinitro-6-cyclopropyl-phenol, 2,4-dinitro-6-cyclobutylphenol, 2,6 dinitro-4-cyclopentylphenol, 2,4 dinitro-6- cyclohexylphenol, 2,4-dinitro-6-phenylphenol and 2,4-dinitro-fi-benzylphenol. By reason of the proven utility as agriculturally useful toxicants of the above listed dinitrophenols and the esters thereof, such as the acetates, crotonates, 3-methyl-2-butenoates and alkyl carbonates, combinations of these compounds with the safening agents of the invention are particularly useful.

To assist those skilled in the art to practice the present invention, the following procedures are suggested by way of illustration parts and percentages being by weight unless otherwise specifically noted.

(1) Nine foliar spray formulations were prepared.

Formulation A contained 400 p.p.m. dinitrocaprylphenol (DNCP), 150 p.p.m. l-(cyclohexyl)-3-(2morpholinyl- (4)-ethyl)-thiourea (CMT) and a carrier consisting of weight percent methanol, 25 weight percent acetone, 49 weight percent water and 1 weight percent glycerin. The other formulations described below contained the same carrier.

Formulation B contained 400 p.p.m. DNCP and 150 p.p.m. Z-tetradecylmercapto-A -imidazoline hydrobromide (TII-IB).

Formulation C contained 400 p.p.m. DNCP and 150 p.p.m. S-t-octylcresoxyethoxyethyl N,N'-dimethylthiuronium chloride (S-OCEDTC).

Formulation D contained 400 p.p.m. DNCP and 150 p.p.m. 2 cetylmercapto-A -imidazoline hydrobromide (CIHB).

Formulation E contained 400 p.p.m. DNCP and 150 p.p.m. 2,3,5-triphenyl tetrazolium chloride ('ITC).

Formulation F contained 400 p.p.m. DNCP and 150 p.p.m. l-acetyl 2 benzylmercapto- A imidazolinc (ABMI).

Formulation G contained 400 p.p.m. DNCP and 150 p.p.m. 2-(B-hydroxyethylmercapto-A -imidazoline hydrochloride (BHMI-H).

Formulation H consisted solely of 400 p.p.m. DNCP in the same carrier described for the other formulations. The formulations were separately sprayed onto nine tomato seedling plants which were about 4 weeks old. The sprayed plants were dried under ambient conditions, placed in the controlled environment of a greenhouse and maintained at about 20-25 C. for about 4 days. The plants were then observed for injury in the form of chemically produced lesions. The injury was reported as either slight, moderate, or severe. The

results of the tests are given in Table I below.

It can be seen from Table I that the tomato plants sprayed with the formulations containing the safening compounds of this invention were only slightly injured; while the plants sprayed with the formulation containing dinitrocaprylphenol without a safening compound were severely injured.

(2) Seven foliar spray formulations were prepared. Each formulation contained the same carrier described in procedure (1) above.

Formulation I contained 400 p.p.m. 2-nonyl-4,6-dinitro phenol (DNNP).

Formulation J contained 400 p.p.m. DNCP.

Formulation K contained 400 p.p.m. DNCP p.p.m CMT.

Formulation L contained 400 p.p.m.

p.p.m CMT.

Formulation M contained 400 p.p.m.

p.p.m. CIHB.

Formulation N contained 400 p.p.m.

p.p.m. TIHB.

Formulation 0 contained 400 p.p.m.

p.p.m. S-OCEDTC.

The formulations were separately sprayed onto the leaves of seven cucumber plants and tested in accordance with the method described in procedure (1) above. The results of the tests are given in Table II below.

and

DNCP and 150 DNCP and 150 DNCP and 150 DNCP and 150 TABLE II Formulation: Injury 1 Severe J Do. K Slight. L Do. M Do. N Do. 0 Do.

It can be seen from Table -II that the cucumber plants sprayed with foliar formulations containing a dinitroalkylphenol without a safening compound were severely injured; while the plants sprayed with a formulation additionally containing a safening compound were only slightly injured.

(3) Two foliar spray formulations were prepared using the same carrier described in procedure (1) above.

Formulation P contained 3 pound DNCP. Formulation Q contained /3 pound DNCP and A; pound CMT.

Formulation P and Q were sprayed onto the foliage of grape plants. Injury tests were carried out in accordance with the method described in procedure (1) above. It can be seen from the following Table HI that the foliage sprayed with the formulation containing a safening compound was only slightly injured.

TABLE III Formulation: Injury P Severe. Q Slight.

(4) Bean powdery mildew control tests were conducted to determine the effect of a safening agent on the biological activityof various dinitrophenol compounds. Eight foliar spray formulations.were,:prepared. ,The carrier .in each formulation was the same as described in procedure 1 above.

Formulation Y contained... 400.:p.p,m. DNNP and 150.

Each spray formulation was separately applied to a separate-bean plant until theleaves of the'plant' were comp1etely"wetted. The foliage *was'd-ried and immediately subjected to inch of artificial rainfall in a fog chamber.-The-. foliage.was then, infected with the powdery.

mildew fungus Erysiphe polygom'. The infected foliage was then placed, in .the controlledenvironment of a greenhouse and maintained at about 20-25 3 C. for 1 days. The results of the powdery mildew control tests, are given in TableiIV below;

TABLE IV Formulation: Percent. control It can be seen from T able: IV that the:addition. of the.

safening agent to the fungicidal formulation did not substantially decrease the fungicidal activity of the dinitrophenol 'compounds. In the case of the formulations, itcanv be rseennthat. the .addition. .of the .safening. agent enhancedi the biological activity. of .DNB P.

Additional. powdery .mildewcontrol. tests were carriedout in accordance.with.the-method..described in procedure (4) above. Seven joliar... spray formulations were prepared. Eachformulationcontained -the. same carrier as describedinf procedure (1) above ,and..400 A p.p.m. DNBP.

Formulation Z consisted solely of the 400i.p.p.-m. DNBP;

and ;the carrier;

addition to-thecarrier and DNBP,

Formulation AA contained 100-p.p.m. TJHB. Formulation AB contained v100 ppm. CIHB. Formulation AC contained 100 p.p.m. S-OCEDTC. Formulation AD contained 100'p .p.m. TTC. Formulation A-E contained 100 ppm. BHMIH. Formulation AF contained 100 ppm. ABMI.

The.,results .of }the,.tes-ts. measuring the percent control ,of

powdery mildew on beanare given in Table .V below.

TABLEV' Formulation: Percent control Y AB 100 AC! 100 It..can be seen from. Table V that in each instance the addition of ,thesafening agent .to thetfungi cidal formula? tion. did not decreasethe 'fungicidalactivityof the ,dinitro:

phenol.

It is understood that changes and ,variations-.may be made without departingfrom-the spiritflandscope. of the invention as definednby the .appendedclaims.v

What is claimed is:

' 1. A fungicidal. composition ,comprisingafungicidally.

eifective amount of avdinitrophenol or the acetate, cro;

ester thereof having .theformula:

tonate, 3-methyl-2-butenoate. or. C 0 alkylcarbonate- (Y) in where-Wis l or 2; and Y is selected fromthe group consisting of alkyl having up to 16- carbon atoms, with the proviso that when n 'is2, the'two alkyl groups'shall total.

no more than '24 carbon atoms; cycloalkyl from 3 to ,6 carbon atoms; isoborny1; phenyl' and benzyl; andythe safening compound 'S-t-octylcresoxyethoxyethyl-N,N-di

methylthiuronium chloride present in an amount sufficient; to reduce the phytotoxic'properties ofthe dinitrophenol,

or its acetate, crotonate, 3-methyl-2-butenoate or:C C alk'yl carbonate ester.

2. A composition "asdefined in claim 1 Wherein'the: weight ratio of safening'compound to dinitrophenol, or acetate, crotonate, 3-methyl-2'-butenoateorCfC alkyl carbonate ester thereof, is from about '1 12. to about 3: 1. 3.;A composition 'as defined in claiml'which-additione ally contains. a carrier .which comprises a mixture 1 of methanol, acetone, water, and glycerine.-.

.4.=A' method rfor reducing injury to crop plant tissues caused. by the external application of fungicidal formula tions-containing a phytotoxic amount of a dinitrophenol, or the acetate, crotonate, 3-methyl--2'-butenoate or C -C alkyl carbonate: esterv thereof, .which comprises applying tothe loci .to beprotectedra fungicidal composition containing as the fungicidal component a dinitrophenohor the acetate,: crotonate; 3-rnethy1-2-butenoate; or. C -C .alkyl carbonateesten thereof; .andnas .a safening compound S-toctylcresoxyethoxyethyl N,N'-dimethylthiuronium chloridepresent in an amount sufliicentqto: reduce the phytotoxic properties of thefungicidal component.-

5. -A method as defined in claim 4 wherein the weight ratio of safeningcompound itoidinitrophenol, or the acetate, crotonate, 3-.methyl-2-butenoate;or,C -C alkyl carbonate ester thereof, is from :about 1:12.to:' about 3:1.

References Cited UNITED STATES PATENTS 2,367,534 1/1945 Smith et al 424326 3,093,666 6/ 1963- Du Brow ,260 564 E 3,334,989 8/1967 Imel et a1. 2 60564 E ALBERT T. MEYERS, Primary Examiner- V. D. TURN-ER, Assistant Examiner us. 01. x11. 

